A genetically informed Registered Report on adverse childhood experiences and mental health

Jessie R. Baldwin; Hannah M. Sallis; Tabea Schoeler; Mark J. Taylor; Alex S.F. Kwong; Jorim J. Tielbeek; Wikus Barkhuizen; Varun Warrier; Laura D. Howe; Andrea Danese; Eamon McCrory; Fruhling Rijsdijk; Henrik Larsson; Sebastian Lundström; Robert Karlsson; Paul Lichtenstein; Marcus Munafò; Jean Baptiste Pingault

doi:10.1038/s41562-022-01482-9

A genetically informed Registered Report on adverse childhood experiences and mental health

Jessie R. Baldwin^*, Hannah M. Sallis, Tabea Schoeler, Mark J. Taylor, Alex S.F. Kwong, Jorim J. Tielbeek, Wikus Barkhuizen, Varun Warrier, Laura D. Howe, Andrea Danese, Eamon McCrory, Fruhling Rijsdijk, Henrik Larsson, Sebastian Lundström, Robert Karlsson, Paul Lichtenstein, Marcus Munafò, Jean Baptiste Pingault

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

25 Citations (Scopus)

Abstract

Children who experience adversities have an elevated risk of mental health problems. However, the extent to which adverse childhood experiences (ACEs) cause mental health problems remains unclear, as previous associations may partly reflect genetic confounding. In this Registered Report, we used DNA from 11,407 children from the United Kingdom and the United States to investigate gene–environment correlations and genetic confounding of the associations between ACEs and mental health. Regarding gene–environment correlations, children with higher polygenic scores for mental health problems had a small increase in odds of ACEs. Regarding genetic confounding, elevated risk of mental health problems in children exposed to ACEs was at least partially due to pre-existing genetic risk. However, some ACEs (such as childhood maltreatment and parental mental illness) remained associated with mental health problems independent of genetic confounding. These findings suggest that interventions addressing heritable psychiatric vulnerabilities in children exposed to ACEs may help reduce their risk of mental health problems.

Original language	English
Pages (from-to)	269-290
Number of pages	22
Journal	Nature Human Behaviour
Volume	7
Issue number	2
DOIs	https://doi.org/10.1038/s41562-022-01482-9
Publication status	Published - Feb 2023

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10.1038/s41562-022-01482-9

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Baldwin, J. R., Sallis, H. M., Schoeler, T., Taylor, M. J., Kwong, A. S. F., Tielbeek, J. J., Barkhuizen, W., Warrier, V., Howe, L. D., Danese, A., McCrory, E., Rijsdijk, F., Larsson, H., Lundström, S., Karlsson, R., Lichtenstein, P., Munafò, M., & Pingault, J. B. (2023). A genetically informed Registered Report on adverse childhood experiences and mental health. Nature Human Behaviour, 7(2), 269-290. https://doi.org/10.1038/s41562-022-01482-9

@article{9ec3209d97254f278be0f5ce0739939a,

title = "A genetically informed Registered Report on adverse childhood experiences and mental health",

abstract = "Children who experience adversities have an elevated risk of mental health problems. However, the extent to which adverse childhood experiences (ACEs) cause mental health problems remains unclear, as previous associations may partly reflect genetic confounding. In this Registered Report, we used DNA from 11,407 children from the United Kingdom and the United States to investigate gene–environment correlations and genetic confounding of the associations between ACEs and mental health. Regarding gene–environment correlations, children with higher polygenic scores for mental health problems had a small increase in odds of ACEs. Regarding genetic confounding, elevated risk of mental health problems in children exposed to ACEs was at least partially due to pre-existing genetic risk. However, some ACEs (such as childhood maltreatment and parental mental illness) remained associated with mental health problems independent of genetic confounding. These findings suggest that interventions addressing heritable psychiatric vulnerabilities in children exposed to ACEs may help reduce their risk of mental health problems.",

author = "Baldwin, {Jessie R.} and Sallis, {Hannah M.} and Tabea Schoeler and Taylor, {Mark J.} and Kwong, {Alex S.F.} and Tielbeek, {Jorim J.} and Wikus Barkhuizen and Varun Warrier and Howe, {Laura D.} and Andrea Danese and Eamon McCrory and Fruhling Rijsdijk and Henrik Larsson and Sebastian Lundstr{\"o}m and Robert Karlsson and Paul Lichtenstein and Marcus Munaf{\`o} and Pingault, {Jean Baptiste}",

note = "Funding Information: We thank all the ALSPAC families who took part in the study, the midwives for their help in recruiting them and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The UK Medical Research Council and Wellcome (grant no. 102215/2/13/2) and the University of Bristol provide core support for ALSPAC data collection. A comprehensive list of grant funding is available on the ALSPAC website. The GWAS data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. Other data used in the preparation of this Article were obtained from the ABCD Study ( https://abcdstudy.org ), held in the NIMH Data Archive (NDA). This is a multisite, longitudinal study designed to recruit more than 10,000 children aged nine to ten and follow them over ten years into early adulthood. The ABCD Study is supported by the National Institutes of Health and additional federal partners under award numbers U01DA041048, U01DA050989, U01DA051016, U01DA041022, U01DA051018, U01DA051037, U01DA050987, U01DA041174, U01DA041106, U01DA041117, U01DA041028, U01DA041134, U01DA050988, U01DA051039, U01DA041156, U01DA041025, U01DA041120, U01DA051038, U01DA041148, U01DA041093, U01DA041089, U24DA041123 and U24DA041147. A full list of supporters is available at https://abcdstudy.org/federal-partners.html . A listing of the participating sites and a complete listing of the study investigators can be found at https://abcdstudy.org/consortium_members/ . ABCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in the analysis or writing of this report. This manuscript reflects the views of the authors and may not reflect the opinions or views of the National Institutes of Health or ABCD consortium investigators. We thank G. Sudre for his support with the QC of the ABCD genetic data. This research was funded in whole or in part by the Wellcome Trust (grant no. 215917/Z/19/Z). For the purpose of open access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. L.D.H. is supported by a Career Development Award fellowship from the UK Medical Research Council (no. MR/M020894/1). H.M.S., A.S.F.K., M.M. and L.D.H. work in a unit that receives funding from the University of Bristol and the UK Medical Research Council (grant nos MC_UU_00011/5 and MC_UU_00011/7). H.M.S. and M.M. are supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at the University Hospitals Bristol National Health Service Foundation Trust and the University of Bristol. M.M. and H.M.S. are members of the UK Centre for Tobacco and Alcohol Studies, a UKCRC Public Health Research: Centre of Excellence. A.D. was funded by the Medical Research Council (grant no. P005918) and by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King{\textquoteright}s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The funders had no role in study design, data analysis, decision to publish or preparation of the manuscript. Funding Information: We thank all the ALSPAC families who took part in the study, the midwives for their help in recruiting them and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The UK Medical Research Council and Wellcome (grant no. 102215/2/13/2) and the University of Bristol provide core support for ALSPAC data collection. A comprehensive list of grant funding is available on the ALSPAC website. The GWAS data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. Other data used in the preparation of this Article were obtained from the ABCD Study (https://abcdstudy.org), held in the NIMH Data Archive (NDA). This is a multisite, longitudinal study designed to recruit more than 10,000 children aged nine to ten and follow them over ten years into early adulthood. Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2023",

month = feb,

doi = "10.1038/s41562-022-01482-9",

language = "English",

volume = "7",

pages = "269--290",

journal = "Nature Human Behaviour",

issn = "2397-3374",

publisher = "Nature Publishing Group",

number = "2",

}

Baldwin, JR , Sallis, HM , Schoeler, T, Taylor, MJ, Kwong, ASF, Tielbeek, JJ, Barkhuizen, W, Warrier, V, Howe, LD, Danese, A, McCrory, E, Rijsdijk, F, Larsson, H, Lundström, S, Karlsson, R, Lichtenstein, P, Munafò, M & Pingault, JB 2023, 'A genetically informed Registered Report on adverse childhood experiences and mental health', Nature Human Behaviour, vol. 7, no. 2, pp. 269-290. https://doi.org/10.1038/s41562-022-01482-9

TY - JOUR

T1 - A genetically informed Registered Report on adverse childhood experiences and mental health

AU - Baldwin, Jessie R.

AU - Sallis, Hannah M.

AU - Schoeler, Tabea

AU - Taylor, Mark J.

AU - Kwong, Alex S.F.

AU - Tielbeek, Jorim J.

AU - Barkhuizen, Wikus

AU - Warrier, Varun

AU - Howe, Laura D.

AU - Danese, Andrea

AU - McCrory, Eamon

AU - Rijsdijk, Fruhling

AU - Larsson, Henrik

AU - Lundström, Sebastian

AU - Karlsson, Robert

AU - Lichtenstein, Paul

AU - Munafò, Marcus

AU - Pingault, Jean Baptiste

N1 - Funding Information: We thank all the ALSPAC families who took part in the study, the midwives for their help in recruiting them and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The UK Medical Research Council and Wellcome (grant no. 102215/2/13/2) and the University of Bristol provide core support for ALSPAC data collection. A comprehensive list of grant funding is available on the ALSPAC website. The GWAS data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. Other data used in the preparation of this Article were obtained from the ABCD Study ( https://abcdstudy.org ), held in the NIMH Data Archive (NDA). This is a multisite, longitudinal study designed to recruit more than 10,000 children aged nine to ten and follow them over ten years into early adulthood. The ABCD Study is supported by the National Institutes of Health and additional federal partners under award numbers U01DA041048, U01DA050989, U01DA051016, U01DA041022, U01DA051018, U01DA051037, U01DA050987, U01DA041174, U01DA041106, U01DA041117, U01DA041028, U01DA041134, U01DA050988, U01DA051039, U01DA041156, U01DA041025, U01DA041120, U01DA051038, U01DA041148, U01DA041093, U01DA041089, U24DA041123 and U24DA041147. A full list of supporters is available at https://abcdstudy.org/federal-partners.html . A listing of the participating sites and a complete listing of the study investigators can be found at https://abcdstudy.org/consortium_members/ . ABCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in the analysis or writing of this report. This manuscript reflects the views of the authors and may not reflect the opinions or views of the National Institutes of Health or ABCD consortium investigators. We thank G. Sudre for his support with the QC of the ABCD genetic data. This research was funded in whole or in part by the Wellcome Trust (grant no. 215917/Z/19/Z). For the purpose of open access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. L.D.H. is supported by a Career Development Award fellowship from the UK Medical Research Council (no. MR/M020894/1). H.M.S., A.S.F.K., M.M. and L.D.H. work in a unit that receives funding from the University of Bristol and the UK Medical Research Council (grant nos MC_UU_00011/5 and MC_UU_00011/7). H.M.S. and M.M. are supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at the University Hospitals Bristol National Health Service Foundation Trust and the University of Bristol. M.M. and H.M.S. are members of the UK Centre for Tobacco and Alcohol Studies, a UKCRC Public Health Research: Centre of Excellence. A.D. was funded by the Medical Research Council (grant no. P005918) and by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The funders had no role in study design, data analysis, decision to publish or preparation of the manuscript. Funding Information: We thank all the ALSPAC families who took part in the study, the midwives for their help in recruiting them and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The UK Medical Research Council and Wellcome (grant no. 102215/2/13/2) and the University of Bristol provide core support for ALSPAC data collection. A comprehensive list of grant funding is available on the ALSPAC website. The GWAS data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. Other data used in the preparation of this Article were obtained from the ABCD Study (https://abcdstudy.org), held in the NIMH Data Archive (NDA). This is a multisite, longitudinal study designed to recruit more than 10,000 children aged nine to ten and follow them over ten years into early adulthood. Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2023/2

Y1 - 2023/2

N2 - Children who experience adversities have an elevated risk of mental health problems. However, the extent to which adverse childhood experiences (ACEs) cause mental health problems remains unclear, as previous associations may partly reflect genetic confounding. In this Registered Report, we used DNA from 11,407 children from the United Kingdom and the United States to investigate gene–environment correlations and genetic confounding of the associations between ACEs and mental health. Regarding gene–environment correlations, children with higher polygenic scores for mental health problems had a small increase in odds of ACEs. Regarding genetic confounding, elevated risk of mental health problems in children exposed to ACEs was at least partially due to pre-existing genetic risk. However, some ACEs (such as childhood maltreatment and parental mental illness) remained associated with mental health problems independent of genetic confounding. These findings suggest that interventions addressing heritable psychiatric vulnerabilities in children exposed to ACEs may help reduce their risk of mental health problems.

AB - Children who experience adversities have an elevated risk of mental health problems. However, the extent to which adverse childhood experiences (ACEs) cause mental health problems remains unclear, as previous associations may partly reflect genetic confounding. In this Registered Report, we used DNA from 11,407 children from the United Kingdom and the United States to investigate gene–environment correlations and genetic confounding of the associations between ACEs and mental health. Regarding gene–environment correlations, children with higher polygenic scores for mental health problems had a small increase in odds of ACEs. Regarding genetic confounding, elevated risk of mental health problems in children exposed to ACEs was at least partially due to pre-existing genetic risk. However, some ACEs (such as childhood maltreatment and parental mental illness) remained associated with mental health problems independent of genetic confounding. These findings suggest that interventions addressing heritable psychiatric vulnerabilities in children exposed to ACEs may help reduce their risk of mental health problems.

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JO - Nature Human Behaviour

JF - Nature Human Behaviour

IS - 2

ER -

A genetically informed Registered Report on adverse childhood experiences and mental health

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